Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo
Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo
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DOI：
10.1073/pnas.201238598
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Lanier, LL
中科院分区：
文献类型：
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作者：
Cerwenka, A;Baron, JL;Lanier, LL
1986年，Karre和他的同事报告说，自然杀伤(NK)细胞拒绝MHC-I类缺陷的肿瘤细胞系(RMA-S)，但如果同一细胞系表达MHC-I类(RMA)，他们不会拒绝。基于这一观察结果，他们提出了NK细胞为“失踪的自我”提供免疫监视的概念，例如，它们清除丢失I类MHC抗原的细胞。这一开创性的观察预测了MHC I类抑制性NK细胞受体的存在。在这里，我们提出证据表明，如果肿瘤表达NKG2D的配体，NK细胞能够排斥表达MHC I类的肿瘤。模拟转染组RMA细胞成瘤。相反，当RMA细胞被转染维A酸早期诱导基因-1伽马或增量(RAE-1)，即激活受体NKG2D的配体时，肿瘤被排斥。肿瘤排斥反应是由NK细胞介导的，而不是CD1限制性NK1.1(+)T细胞。在排斥RAE-1转基因肿瘤的动物中，没有产生针对亲本肿瘤的T细胞介导的免疫记忆，这些动物在与亲本RMA肿瘤的再次挑战中屈服。因此，NK细胞能够排斥表达RAE-1分子的肿瘤，尽管肿瘤上表达自身的MHC I类分子，这表明NK细胞参与了对含有I类分子的恶性肿瘤的免疫。
In 1986, Karre and colleagues reported that natural killer (NK) cells rejected an MHC class I-deficient tumor cell line (RMA-S) but they did not reject the same cell line if it expressed MHC class I (RMA). Based on this observation, they proposed the concept that NK cells provide immune surveillance for "missing self," e.g., they eliminate cells that have lost class I MHC antigens. This seminal observation predicted the existence of inhibitory NK cell receptors for MHC class I. Here, we present evidence that NK cells are able to reject tumors expressing MHC class I if the tumor expresses a ligand for NKG2D. Mock-transfected RMA cells resulted in tumor formation. In contrast, when RMA cells were transfected with the retinoic acid early inducible gene-1 gamma or delta (RAE-1), ligands for the activating receptor NKG2D, the tumors were rejected. The tumor rejection was mediated by NK cells, and not by CD1-restricted NK1.1(+) T cells. No T cell-mediated immunological memory against the parental tumor was generated in the animals that had rejected the RAE-1 transfected tumors, which succumbed to rechallenge with the parental RMA tumor. Therefore, NK cells are able to reject a tumor expressing RAE-1 molecules, despite expression of self MHC class I on the tumor, demonstrating the potential for NK cells to participate in immunity against class I-bearing malignancies.